Target-specific liposomes have been studied extensively for their use as inert carriers for drugs, enzymes, hormones, DNA and other biomedically important substances (for recent reviews see Connor et al., Pharm Ther., 28: 341-365 (1985). Immunoliposomes have been shown to bind specifically to their target cells in vitro and in vivo. The subsequent events which follow cell binding are currently of great interest since liposome binding may not necessarily be followed by the delivery of the encapsulated drug into the target cell.
One approach to ensure target-specific delivery of drugs into the cell is to fuse liposomes with intact cells. This approach has been demonstrated using a variety of fusogens such as Sendai virus (Okada, Exp. Cell Res., 26: 98-107 (1962), Nakanishi et al., Exp. Cell Res., 159: 399-409 (1985)); synexin (Hong et al., Proc. Natl. Acad. Sci. U.S.A., 79: 4642-4644 (1982)); and polyethyleneglycol (Boni et al., Biochem. Biophys. Acta., 775: 409-418 (1984), as well as fusion by means of pulsed electric field (Vienken & Zimmerman, FEBS Letts., 182: 278-280 (1985).
However, all of these fusion protocols suffer from a relatively high cytotoxicity to the target cells. An alternative approach for drug intake is to exploit cellular endocytosis. Using pH-sensitive immunoliposomes, which become fusion competent at pH below 6.5 and fuse with endosomes, this approach was successful for cytoplasmic delivery of antitumor drugs (Connor & Huang, J. Cell. Biol., 101: 582-589, (1985). However, an endocytosis-dependent drug delivery system may not be applicable to target cells with low endocytotic activity.
To overcome this constraint, heat-sensitive immunoliposomes were developed (Sullivan & Huang, Biochim. Biophys. Acta., 812: 116-126 (1985). This cell delivery system depends on the uptake of drug released from briefly heated cell bound liposomes. For example, enhanced uptake of .sup.3 H-uridine encapsulated in heat-sensitive immunoliposomes composed of dipalmitoyl phosphatidylcholine (DPPC) was reported recently (see for example, Sullivan & Huang , PNAS USA, 83:6117-6121 (1986)).
Although this heat-sensitive system was quite efficient, the localized heating of liposome treated cells may not be feasible for many applications, particularly in vivo situations.